G Guyatt

A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group.

BACKGROUND Critically ill patients who require mechanical ventilation are at increased risk for gastrointestinal bleeding from stress ulcers. There are conflicting data on the effect of histamine H2-receptor antagonists and the cytoprotective agent sucralfate on rates of gastrointestinal bleeding, ventilator-associated pneumonia, and mortality. METHODS In a multicenter, randomized, blinded, placebo-controlled trial, we compared sucralfate with the H2-receptor antagonist ranitidine for the prevention of upper gastrointestinal bleeding in 1200 patients who required mechanical ventilation. Patients received either nasogastric sucralfate suspension (1 g every six hours) and an intravenous placebo or intravenous ranitidine (50 mg every eight hours) and a nasogastric placebo. RESULTS The patients in the two groups had similar base-line characteristics. Clinically important gastrointestinal bleeding developed in 10 of 596 (1.7 percent) of the patients receiving ranitidine, as compared with 23 of 604 (3.8 percent) of those receiving sucralfate (relative risk, 0.44; 95 percent confidence interval, 0.21 to 0.92; P=0.02). In the ranitidine group, 114 of 596 patients (19.1 percent) had ventilator-associated pneumonia, as compared with 98 of 604 (16.2 percent) in the sucralfate group (relative risk, 1.18; 95 percent confidence interval, 0.92 to 1.51; P=0.19). There was no significant difference between the groups in mortality in the intensive care unit (ICU) (23.5 percent in the ranitidine group and 22.9 percent in the sucralfate group) or the duration of the stay in the ICU (median, nine days in both groups). CONCLUSIONS Among critically ill patients requiring mechanical ventilation, those receiving ranitidine had a significantly lower rate of clinically important gastrointestinal bleeding than those treated with sucralfate. There were no significant differences in the rates of ventilator-associated pneumonia, the duration of the stay in the ICU, or mortality.

Development of a disease specific questionnaire to measure health related quality of life in patients with chronic liver disease

BACKGROUND AND AIMS To develop and assess a disease specific instrument for measuring health related quality of life (HRQL) in patients with chronic liver disease (CLD). METHODS Based on responses from 60 patients with chronic liver disease, from 20 liver experts, and from a Medline search of the literature, items potentially affecting the HRQL of these patients were identified. A separate sample of 75 patients identified which items they found problematic and rated their importance. Results were explored using factor analysis; domains were chosen and items placed within domains. Redundant questions were eliminated and the final questionnaire was pretested in 10 patients. Using this instrument, HRQL was assessed in a further 133 patients with various types and stages of liver disease. RESULTS Patients, experts, and the literature search identified 156 items of potential importance. Of these, 35 proved important to over 50% of 75 respondents in the item reduction sample. The factor analysis suggested six domains. After eliminating redundancies, the Chronic Liver Disease Questionnaire (CLDQ) included 29 items in the following domains: fatigue, activity, emotional function, abdominal symptoms, systemic symptoms, and worry. In pretesting, patients found the CLDQ clear and easy to complete in 10 minutes. In another 133 patients, the CLDQ showed a gradient between patients without cirrhosis, Child’s A cirrhosis, and those with Child’s B or C cirrhosis. CLDQ has evidence for moderate reliability at six months and seems to be responsive. CONCLUSION The CLDQ is short, easy to administer, produces both a summary score and domain scores, and correlates with the severity of liver disease.

The impact of measuring patient-reported outcomes in clinical practice: a systematic review of the literature

ObjectiveThe purpose of this paper is to summarize the best evidence regarding the impact of providing patient-reported outcomes (PRO) information to health care professionals in daily clinical practice.MethodsSystematic review of randomized clinical trials (Medline, Cochrane Library; reference lists of previous systematic reviews; and requests to authors and experts in the field).ResultsOut of 1,861 identified references published between 1978 and 2007, 34 articles corresponding to 28 original studies proved eligible. Most trials (19) were conducted in primary care settings performed in the USA (21) and assessed adult patients (25). Information provided to professionals included generic health status (10), mental health (14), and other (6). Most studies suffered from methodologic limitations, including analysis that did not correspond with the unit of allocation. In most trials, the impact of PRO was limited. Fifteen of 23 studies (65%) measuring process of care observed at least one significant result favoring the intervention, as did eight of 17 (47%) that measured outcomes of care.ConclusionsMethodological concerns limit the strength of inference regarding the impact of providing PRO information to clinicians. Results suggest great heterogeneity of impact; contexts and interventions that will yield important benefits remain to be clearly defined.

Aspirin in patients undergoing noncardiac surgery

BACKGROUND There is substantial variability in the perioperative administration of aspirin in patients undergoing noncardiac surgery, both among patients who are already on an aspirin regimen and among those who are not. METHODS Using a 2-by-2 factorial trial design, we randomly assigned 10,010 patients who were preparing to undergo noncardiac surgery and were at risk for vascular complications to receive aspirin or placebo and clonidine or placebo. The results of the aspirin trial are reported here. The patients were stratified according to whether they had not been taking aspirin before the study (initiation stratum, with 5628 patients) or they were already on an aspirin regimen (continuation stratum, with 4382 patients). Patients started taking aspirin (at a dose of 200 mg) or placebo just before surgery and continued it daily (at a dose of 100 mg) for 30 days in the initiation stratum and for 7 days in the continuation stratum, after which patients resumed their regular aspirin regimen. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days. RESULTS The primary outcome occurred in 351 of 4998 patients (7.0%) in the aspirin group and in 355 of 5012 patients (7.1%) in the placebo group (hazard ratio in the aspirin group, 0.99; 95% confidence interval [CI], 0.86 to 1.15; P=0.92). Major bleeding was more common in the aspirin group than in the placebo group (230 patients [4.6%] vs. 188 patients [3.8%]; hazard ratio, 1.23; 95% CI, 1.01, to 1.49; P=0.04). The primary and secondary outcome results were similar in the two aspirin strata. CONCLUSIONS Administration of aspirin before surgery and throughout the early postsurgical period had no significant effect on the rate of a composite of death or nonfatal myocardial infarction but increased the risk of major bleeding. (Funded by the Canadian Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number, NCT01082874.).

Using and understanding sedation scoring systems: a systematic review

Objective: To systematically review instruments for measuring the level and effectiveness of sedation in adult and pediatric ICU patients.¶Study identification: We searched MEDLINE, EMBASE, the Cochrane Library and reference lists of the relevant articles. We selected studies if the sedation instrument reported items related to consciousness and one or more additional items related to the effectiveness or side effects of sedation.¶Data abstraction: We extracted data on the description of the instrument and on their measurement properties (internal consistency, reliability, validity and responsiveness).¶Results: We identified 25 studies describing relevant sedation instruments. In addition to the level of consciousness, agitation and synchrony with the ventilator were the most frequently assessed aspects of sedation. Among the 25 instruments, one developed in pediatric ICU patients (the Comfort Scale), and 3 developed in adult ICU patients (the Ramsay scale, the Sedation-Agitation-Scale and the Motor Activity Assessment Scale), were tested for both reliability and validity. None of these instruments were tested for their ability to detect change in sedation status over time (responsiveness).¶Conclusion: Many instruments have been used to measure sedation effectiveness in ICU patients. However, few of them exhibit satisfactory clinimetric properties. To help clinicians assess sedation at the bedside, to aid readers critically appraise the growing number of sedation studies in the ICU literature, and to inform the design of future investigations, additional information about the measurement properties of sedation effectiveness instruments is needed.

Enteral nutrition in the critically ill patient : a prospective survey

OBJECTIVES To describe current enteral nutrition-prescribing practices for critically ill patients, and to identify factors associated with initiation of, and tolerance to, enteral nutrition. DESIGN A prospective, cohort study. SETTING Two tertiary care medical-surgical intensive care units (ICU) in Ontario, Canada. PATIENTS We enrolled 99 consecutive patients who were expected to stay in the ICU for > 3 days and who were unable to tolerate oral nutrition. We followed patients for 21 days or until they tolerated enteral nutrition, tolerated oral nutrition, were discharged from the ICU, or died. MEASUREMENTS AND MAIN RESULTS We recorded time elapsed from ICU admission to initiation and tolerance of enteral feedings, and examined factors associated with these events. We defined tolerance as receiving 90% of estimated daily energy requirements for > 48 hrs without gastrointestinal dysfunction (i.e., high gastric residuals, vomiting, diarrhea, abdominal distention). Seventy-three (74%) of 99 patients were started on enteral feedings an average 3.1 days (range 1 to 18) after ICU admission. Of 26 patients never started on enteral nutrition, three (12.5%) patients eventually tolerated oral nutrition, 14 (54.0%) patients were discharged from the ICU, and seven (27.0%) patients died. Reasons for not initiating enteral nutrition included absence of bowel sounds (27.0%), high nasogastric drainage (16.9%), contraindication to enteral nutrition (16.7%), tolerance of oral nutrition (6.8%), and no apparent reason (5.1%). Abdominal surgery, use of vasoactive drugs, and admission to one hospital made initiation of enteral nutrition less likely, whereas presence of bowel sounds and admission to the other hospital made initiation of enteral nutrition more likely. Thirty-five (42.9%) of 73 patients started on enteral nutrition achieved tolerance of the regimen. The average time from ICU admission to tolerance of feedings was 5.8 days (range 1 to 14). Once started on enteral nutrition, the most common reasons for decreasing or discontinuing feedings included high gastric residuals (51.0%), mechanical feeding tube problems (15.4%), medical or surgical procedures (5.4%), and vomiting (5.1%). Use of paralytic agents and the presence of high gastric residuals were associated with intolerance. Of 38 patients who did not achieve tolerance, 20 (52.6%) patients were discharged from the ICU, eight (21.0%) patients died, and eight (21.0%) patients eventually tolerated oral nutrition. CONCLUSIONS Enteral nutrition is not started in all eligible ICU patients. Approximately half of those patients receiving enteral nutrition achieved tolerance of the regimen. Gastrointestinal dysfunction causing intolerance to enteral nutrition is a common reason for not starting, or discontinuing, feedings.

Myocardial injury after noncardiac surgery: a large, international, prospective cohort study establishing diagnostic criteria, characteristics, predictors, and 30-day outcomes.

Background:Myocardial injury after noncardiac surgery (MINS) was defined as prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days after noncardiac surgery. The study’s four objectives were to determine the diagnostic criteria, characteristics, predictors, and 30-day outcomes of MINS. Methods:In this international, prospective cohort study of 15,065 patients aged 45 yr or older who underwent in-patient noncardiac surgery, troponin T was measured during the first 3 postoperative days. Patients with a troponin T level of 0.04 ng/ml or greater (elevated “abnormal” laboratory threshold) were assessed for ischemic features (i.e., ischemic symptoms and electrocardiography findings). Patients adjudicated as having a nonischemic troponin elevation (e.g., sepsis) were excluded. To establish diagnostic criteria for MINS, the authors used Cox regression analyses in which the dependent variable was 30-day mortality (260 deaths) and independent variables included preoperative variables, perioperative complications, and potential MINS diagnostic criteria. Results:An elevated troponin after noncardiac surgery, irrespective of the presence of an ischemic feature, independently predicted 30-day mortality. Therefore, the authors’ diagnostic criterion for MINS was a peak troponin T level of 0.03 ng/ml or greater judged due to myocardial ischemia. MINS was an independent predictor of 30-day mortality (adjusted hazard ratio, 3.87; 95% CI, 2.96–5.08) and had the highest population-attributable risk (34.0%, 95% CI, 26.6–41.5) of the perioperative complications. Twelve hundred patients (8.0%) suffered MINS, and 58.2% of these patients would not have fulfilled the universal definition of myocardial infarction. Only 15.8% of patients with MINS experienced an ischemic symptom. Conclusion:Among adults undergoing noncardiac surgery, MINS is common and associated with substantial mortality.

Dalteparin versus unfractionated heparin in critically ill patients.

BACKGROUND The effects of thromboprophylaxis with low-molecular-weight heparin, as compared with unfractionated heparin, on venous thromboembolism, bleeding, and other outcomes are uncertain in critically ill patients. METHODS In this multicenter trial, we tested the superiority of dalteparin over unfractionated heparin by randomly assigning 3764 patients to receive either subcutaneous dalteparin (at a dose of 5000 IU once daily) plus placebo once daily (for parallel-group twice-daily injections) or unfractionated heparin (at a dose of 5000 IU twice daily) while they were in the intensive care unit. The primary outcome, proximal leg deep-vein thrombosis, was diagnosed on compression ultrasonography performed within 2 days after admission, twice weekly, and as clinically indicated. Additional testing for venous thromboembolism was performed as clinically indicated. Data were analyzed according to the intention-to-treat principle. RESULTS There was no significant between-group difference in the rate of proximal leg deep-vein thrombosis, which occurred in 96 of 1873 patients (5.1%) receiving dalteparin versus 109 of 1873 patients (5.8%) receiving unfractionated heparin (hazard ratio in the dalteparin group, 0.92; 95% confidence interval [CI], 0.68 to 1.23; P=0.57). The proportion of patients with pulmonary emboli was significantly lower with dalteparin (24 patients, 1.3%) than with unfractionated heparin (43 patients, 2.3%) (hazard ratio, 0.51; 95% CI, 0.30 to 0.88; P=0.01). There was no significant between-group difference in the rates of major bleeding (hazard ratio, 1.00; 95% CI, 0.75 to 1.34; P=0.98) or death in the hospital (hazard ratio, 0.92; 95% CI, 0.80 to 1.05; P=0.21). In prespecified per-protocol analyses, the results were similar to those of the main analyses, but fewer patients receiving dalteparin had heparin-induced thrombocytopenia (hazard ratio, 0.27; 95% CI, 0.08 to 0.98; P=0.046). CONCLUSIONS Among critically ill patients, dalteparin was not superior to unfractionated heparin in decreasing the incidence of proximal deep-vein thrombosis. (Funded by the Canadian Institutes of Health Research and others; PROTECT ClinicalTrials.gov number, NCT00182143.).

Enteral nutrition in the critically ill patient: A critical review of the evidence

ObjectiveTo examine the relationship between enteral nutrition (EN) and infection in the critically ill.Setting: Computerized search of published research and review of relevant reference lists.Study selection: 151 citations were reviewed and 39 articles met selection criteria. Primary studies were included if they evaluated EN in critically ill humans and its effect on infectious morbidity and mortality.Measurements and resultsRelevant data were abstracted on the timing and impact of EN on morbidity, the optimal route of administration, composition and pH of EN, and bacterial contamination of EN. The evidence from human studies that EN, particularly early EN, results in reduced septic morbidity as compared to parenteral nutrition is limited to small, unblinded studies with non-rigorous definitions of pneumonia. There is no evidence to support a preference of feeding into the stomach versus the small bowel. The addition of fish oil, arginine, glutamine and fiber to enteral feeds has a variable impact on survival in animal models; there are no trials in critically ill patients that demonstrate a reduction in infectious morbidity and mortality. Acidification of enteral nutrition results in decreased bacterial colonization of the stomach in critically ill patients. Bacterial contamination of enteral nutrition is an important source of infection.ConclusionsEvidence from experimental data in critically ill patients suggests that enteral nutrition may have a favourable impact on gastrointestinal immunological function and infectious morbidity.

Clonidine in Patients Undergoing Noncardiac Surgery

BACKGROUND Marked activation of the sympathetic nervous system occurs during and after noncardiac surgery. Low-dose clonidine, which blunts central sympathetic outflow, may prevent perioperative myocardial infarction and death without inducing hemodynamic instability. METHODS We performed a blinded, randomized trial with a 2-by-2 factorial design to allow separate evaluation of low-dose clonidine versus placebo and low-dose aspirin versus placebo in patients with, or at risk for, atherosclerotic disease who were undergoing noncardiac surgery. A total of 10,010 patients at 135 centers in 23 countries were enrolled. For the comparison of clonidine with placebo, patients were randomly assigned to receive clonidine (0.2 mg per day) or placebo just before surgery, with the study drug continued until 72 hours after surgery. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days. RESULTS Clonidine, as compared with placebo, did not reduce the number of primary-outcome events (367 and 339, respectively; hazard ratio with clonidine, 1.08; 95% confidence interval [CI], 0.93 to 1.26; P=0.29). Myocardial infarction occurred in 329 patients (6.6%) assigned to clonidine and in 295 patients (5.9%) assigned to placebo (hazard ratio, 1.11; 95% CI, 0.95 to 1.30; P=0.18). Significantly more patients in the clonidine group than in the placebo group had clinically important hypotension (2385 patients [47.6%] vs. 1854 patients [37.1%]; hazard ratio 1.32; 95% CI, 1.24 to 1.40; P<0.001). Clonidine, as compared with placebo, was associated with an increased rate of nonfatal cardiac arrest (0.3% [16 patients] vs. 0.1% [5 patients]; hazard ratio, 3.20; 95% CI, 1.17 to 8.73; P=0.02). CONCLUSIONS Administration of low-dose clonidine in patients undergoing noncardiac surgery did not reduce the rate of the composite outcome of death or nonfatal myocardial infarction; it did, however, increase the risk of clinically important hypotension and nonfatal cardiac arrest. (Funded by the Canadian Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number, NCT01082874.).